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Diabetic retinopathy (DR) and age‐related macular degeneration (AMD) are two important leading causes of acquired blindness in developed countries. As accumulation of advanced glycation end products (AGEs) in retinal pigment epithelial (RPE) cells plays an important role in both DR and AMD, and the methylglyoxal (MGO) within the AGEs exerts irreversible effects on protein structure and function, it is crucial to understand the underlying mechanism of MGO‐induced RPE cell death. Using ARPE‐19 as the cell model, this study revealed that MGO induces RPE cell death through a caspase‐independent manner, which relying on reactive oxygen species (ROS) formation, mitochondrial membrane potential (MMP) loss, intracellular calcium elevation and endoplasmic reticulum (ER) stress response. Suppression of ROS generation can reverse the MGO‐induced ROS production, MMP loss, intracellular calcium increase and cell death. Moreover, store‐operated calcium channel inhibitors MRS1845 and YM‐58483, but not the inositol 1,4,5‐trisphosphate (IP3) receptor inhibitor xestospongin C, can block MGO‐induced ROS production, MMP loss and sustained intracellular calcium increase in ARPE‐19 cells. Lastly, inhibition of ER stress by salubrinal and 4‐PBA can reduce the MGO‐induced intracellular events and cell death. Therefore, our data indicate that MGO can decrease RPE cell viability, resulting from the ER stress‐dependent intracellular ROS production, MMP loss and increased intracellular calcium increase. As MGO is one of the components of drusen in AMD and is the AGEs adduct in DR, this study could provide a valuable insight into the molecular pathogenesis and therapeutic intervention of AMD and DR.

This study aimed to investigate the effects of Shuanglongjiegu pill (SLJGP) on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and explore its mechanism based on miR-217/RUNX2 axis. Results found that drug-containing serum of SLJGP promoted BMSCs viability with a dose-dependent effect. Under osteogenic differentiation conditions, SLJGP promoted the expression of ALP, OPN, BMP2, RUNX2, and the osteogenic differentiation ability of BMSCs. In addition, SLJGP significantly reduced miR-217 expression, and miR-217 directly targeted RUNX2. After treatment with miR-217 mimic, the promoting effects of SLJGP on proliferation and osteogenic differentiation of BMSCs were significantly inhibited. MiR-217 mimic co-treated with pcDNA-RUNX2 further confirmed that the miR-217/RUNX2 axis was involved in SLJGP to promote osteogenic differentiation of BMSCs. In addition, analysis of Wnt/β-catenin pathway protein expression showed that SLJGP activated the Wnt/β-catenin pathway through miR-217/RUNX2. In conclusion, SLJGP promoted osteogenic differentiation of BMSCs by regulating miR-217/RUNX2 axis and activating Wnt/β-catenin pathway.

This study aimed to investigate the effects of Shuanglongjiegu pill (SLJGP) on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and explore its mechanism based on miR-217/RUNX2 axis. Results found that drug-containing serum of SLJGP promoted BMSCs viability with a dose-dependent effect. Under osteogenic differentiation conditions, SLJGP promoted the expression of ALP, OPN, BMP2, RUNX2, and the osteogenic differentiation ability of BMSCs. In addition, SLJGP significantly reduced miR-217 expression, and miR-217 directly targeted RUNX2. After treatment with miR-217 mimic, the promoting effects of SLJGP on proliferation and osteogenic differentiation of BMSCs were significantly inhibited. MiR-217 mimic co-treated with pcDNA-RUNX2 further confirmed that the miR-217/RUNX2 axis was involved in SLJGP to promote osteogenic differentiation of BMSCs. In addition, analysis of Wnt/[beta]-catenin pathway protein expression showed that SLJGP activated the Wnt/[beta]-catenin pathway through miR-217/RUNX2. In conclusion, SLJGP promoted osteogenic differentiation of BMSCs by regulating miR-217/RUNX2 axis and activating Wnt/[beta]-catenin pathway.

Artificial photosynthesis of urea from NH 3 and CO 2 seems to remain still essentially unexplored. Herein, three isomorphic three-dimensional covalent organic frameworks with twofold interpenetrated ffc topology are functionalized by benzene, pyrazine, and tetrazine active moieties, respectively. A series of experiment results disclose the gradually enhanced conductivity, light-harvesting capacity, photogenerated carrier separation efficiency, and co-adsorption capacity towards NH 3 and CO 2 in the order of benzene-, pyrazine-, and tetrazine-containing framework. This in turn endows tetrazine-containing framework with superior photocatalytic activity towards urea production from NH 3 and CO 2 with the yield of 523 μmol g −1 h −1 , 40 and 4 times higher than that for benzene- and pyrazine-containing framework, respectively, indicating the heterocyclic N microenvironment-dependent catalytic performance for these three photocatalysts. This is further confirmed by in-situ spectroscopic characterization and density functional theory calculations. This work lays a way towards sustainable photosynthesis of urea. Artificial photosynthesis of urea from NH 3 and CO 2 remains difficult to achieve. Herein, by three altering the number of heterocyclic N atoms within a series of covalent organic frameworks, the authors report an increase in urea photosynthesis yields and efficiencies.

Understanding precise structures of two-/three- dimensional (2D/3D) covalent organic polymers (COPs) through single-crystal X-ray diffraction (SCXRD) analysis is important. However, how to grow high-quality single crystals for 2D/3D COPs is of challenge due to poor reversibility and difficult self-correction of covalent bonds. In addition, the success of introducing tellurium into the backbone to construct 2D/3D COPs and obtaining their single crystals is rare. Here, utilizing the strategy that a heavy element (e.g., tellurium) can form dynamic linkages with a self-correction function, we develop a fast and universal method for growing large-sized single crystals (up to 500 µm) for 2D/3D COPs, especially for 2D COPs. Three 2D COPs and one 3D COP are harvested through dynamic -Te-O-P- bonds in two days, with structures clearly uncovered via the SCXRD analysis. These 2D/3D COPs also show promising photocatalytic activities (nearly 100% selectivity and 100% yield) in superoxide anion radical-mediated coupling of (arylmethyl)amines. Understanding precise structures of two-/three- dimensional covalent organic polymers through single-crystal X-ray diffraction analysis is interesting however, to grow high-quality single crystals of these materials is challenging. Here, the authors incorporate tellurium into the backbones covalent organic polymers as a concise and fast method to grow large single crystals.

It has been reported that the normal adults can suffer from an intracranial aneurysm (IA) that might present the risk of rupture and cause the subarachnoid hemorrhage. Peroxisome proliferator-activated receptor-γ (PPAR-γ) as a nuclear hormone receptor has been identified to involve in the progress of the formation and rupture of IAs. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect PPAR-γmRNA expression in the macrophages of the patients with IAs. The information including fasting blood glucose (FBG), interleukin-6 (IL-6), and systolic blood pressure (SBP) were collected. The aneurysm parameters of all the participants were obtained through the cerebral angiography. Establishing the receiver-operating characteristic curve (ROC curve) evaluated the clinical significances of PPAR-γmRNA for IAs rupture. In this study, we observed that the rupture of IAs was caused by the maximum height of aneurysm ⩾7 mm, the location of aneurysm in posterior communicating artery (PCOM) or anterior communicating artery (ACOM), and the increase of aneurysm size ratio (SR). The levels of SBP and IL-6 in the rupture group were higher than those in the unrupture group, and PPAR-γmRNA expression in the rupture group was also significantly reduced. In addition, heavy drinking was statistically significant between the ruptured and unruptured groups. There was no significant difference in serum FBG level between the two groups. The evidences of this study showed that PPAR-γmRNA was negatively correlated with SBP, SR, and IL-6 levels in rupture group, respectively. The AUC of PPAR-γmRNA in ROC curve was 0.867, indicating that the change of PPAR-γmRNA level had obvious effect on IAs rupture. The aim of this study was to evaluate the potential of PPAR-γ in macrophages to prevent IAs rupture.

ObjectiveTo investigate the distribution of aetiologies and outcomes in neonates with prolonged neonatal jaundice.DesignAn observational study.SettingMultiple tertiary centres from the China Neonatal Genome Project.PatientsTerm infants with jaundice lasting more than 14 days or preterm infants with jaundice lasting more than 21 days were recruited between 1 June 2016 and 30 June 2020.Main outcome measuresAetiology and outcomes were recorded from neonates with prolonged unconjugated hyperbilirubinaemia (PUCHB) and prolonged conjugated hyperbilirubinaemia (PCHB).ResultsA total of 939 neonates were enrolled, and known aetiologies were identified in 84.1% of neonates (790 of 939). Among 411 neonates with PCHB, genetic disorders (27.2%, 112 of 411) were the leading aetiologies. There were 8 deceased neonates, 19 neonates with liver failure and 12 with neurodevelopmental delay. Among 528 neonates with PUCHB, a genetic aetiology was identified in 2 of 219 neonates (0.9%) who showed disappearance of jaundice within 4 weeks of age and in 32 of 309 neonates (10.4%) with persistent jaundice after 4 weeks of age. A total of 96 of 181 neonates (53.0%) who received genetic diagnoses had their clinical diagnosis modified as a result of the genetic diagnoses.ConclusionKnown aetiologies were identified in approximately 80% of neonates in our cohort, and their overall outcomes were favourable. Genetic aetiology should be considered a priority in neonates with PCHB or the persistence of jaundice after 4 weeks of age. Moreover, genetic data can modify the clinical diagnosis and guide disease management, potentially improving outcomes.

By using silver nanoplatelets with a widely tunable localized surface plasmon resonance (LSPR) and their corresponding local field enhancement, here we show large manipulation of plasmonic enhanced upconversion in NaYF4:Yb 3+ /Er 3+ nanocrystals at the single particle level. In particular, we show that when the plasmonic resonance of silver nanolplatelets is tuned to 656 nm, matching the emission wavelength, an upconversion enhancement factor ~5 is obtained. However, when the plasmonic resonance is tuned to 980 nm, matching the nanocrystal absorption wavelength, we achieve an enhancement factor of ~22 folds. The precise geometric arrangement between fluorescent nanoparticles and silver nanoplatelets allows us to make, for the first time, a comparative analysis between experimental results and numerical simulations, yielding a quantitative agreement at the single particle level. Such a comparison lays the foundations for a rational design of hybrid metal-fluorescent nanocrystals to harness the upconversion enhancement for biosensing and light harvesting applications.

By using silver nanoplatelets with a widely tunable localized surface plasmon resonance (LSPR), and their corresponding local field enhancement, here we show large manipulation of plasmonic enhanced upconversion in NaYF4:Yb(3+)/Er(3+) nanocrystals at the single particle level. In particular, we show that when the plasmonic resonance of silver nanolplatelets is tuned to 656 nm, matching the emission wavelength, an upconversion enhancement factor ~5 is obtained. However, when the plasmonic resonance is tuned to 980 nm, matching the nanocrystal absorption wavelength, we achieve an enhancement factor of ~22 folds. The precise geometric arrangement between fluorescent nanoparticles and silver nanoplatelets allows us to make, for the first time, a comparative analysis between experimental results and numerical simulations, yielding a quantitative agreement at the single particle level. Such a comparison lays the foundations for a rational design of hybrid metal-fluorescent nanocrystals to harness the upconversion enhancement for biosensing and light harvesting applications.

Nonisothermal crystallization of high density polyethylene (HDPE)/maleic anhydride‐modified HDPE(manPE)/nanoscale calcium carbonate (CaCO3) nanocomposite was investigated by means of wide angle X‐ray diffraction (WAXD), polarized optical microscopy (POM), and differential scanning calorimetry (DSC). WAXD indicated that the crystallinity was reduced with the addition of CaCO3. The spherulite size of HDPE increased in the presence of manPE, but decreased when CaCO3 was added from observation of POM. A modified Avrami analysis, Ozawa analysis, and Liu analysis were applied to the nonisothermal crystallization process. Crystallizability followed the order: HDPE/manPE/CaCO3 > HDPE/CaCO3 > HDPE/manPE > HDPE when undercooling was taken into account. Dependence of the effective activation energy on the relative crystallinity was estimated by the Friedman equation, and the results were used to calculate the parameters (Kg and U*) of Lauritzen‐Hoffman's equation by Vyazovkin's method. These results indicate that the addition of maleic anhydride groups and CaCO3 tend to promote the nucleation of spherulites on their surfaces and lead to epitaxial growth of the crystallites. But at the same time, manPE and CaCO3 particles may hinder the transport of the molecule chains resulting in a decrease of the crystallization growth rate. POLYM. ENG. SCI., 2008. © 2008 Society of Plastics Engineers